AKI-to-CKD transition is a potential mechanism for non-albuminuric diabetic kidney disease.

Although albuminuria development is considered the natural course of diabetic kidney disease (DKD), increasing evidence indicate that the disease can present as non-albuminuric DKD (NA-DKD), characterized by prominent tubulointerstitial injury and fibrosis without obvious glomerulopathy. However, the pathogenic mechanisms underlying NA-DKD remain unclear. As diabetic patients are more susceptible to acute kidney injury (AKI), and the maladaptive repair of kidney tubules following AKI occurs more frequently in diabetic than non-diabetic patients, the enhanced AKI-to-CKD transition may be a significant contributor of NA-DKD. Recent studies indicate that endoplasmic reticulum (ER) stress is a key pathogenic driver of AKI-to-CKD transition, and that the tubular expression of ER-resident protein reticulon 1A (RTN1A) correlates with human DKD progression and AKI-to-CKD transition. Experimental studies showed that RTN1A indeed mediates tubular cell injury and AKI-to-CKD transition in diabetic mice via concomitant activation of ER stress and mitochondrial dysfunction as a mediator of ER-mitochondrial crosstalk. Further understanding of the pathogenesis of tubular injury in DKD will help us to develop sensitive and specific biomarkers or diagnostic tools to distinguish between injury-related AKI, pre-renal AKI from hemodynamic changes, and the progression of DKD in order to better manage patients with DKD.